Characterization of imidacloprid-induced hepatotoxicity and its mechanisms based on a metabolomic approach in Xenopus laevis.

The toxic effects of imidacloprid are attracting increased concern because of its widespread use in agriculture and its persistence in the aquatic environment. Imidacloprid bioaccumulates and triggers various morphological and behavioral responses in amphibians, but the toxic effects and mechanism of imidacloprid in amphibians remain uncertain. In this study, the acute toxicity and chronic effects of imidacloprid on Xenopus laevis were studied. Acute toxicity for 96 h revealed that imidacloprid had an LC50 value of 74.18 mg/L. After exposure for 28 d under 1/10 and 1/100 LC50, liver samples from X. laevis were employed for biochemical analyses, pathological studies, and nontargeted metabolomics to systematically assess the toxic effects and mechanisms of imidacloprid. The results showed that oxidative stress and hepatic tissue morphology changes were observed in treated X. laevis liver. Twelve metabolites involved in metabolic pathway were altered between the control and high exposure groups and twenty-one metabolites were altered between the control and low exposure group. Eight metabolic pathways exposed to high levels and nine metabolic pathways exposed to low level of imidacloprid were disturbed. These pathways were primarily related to amino acid metabolism, lipid metabolism, and nucleotide metabolism. Our research provides essential information to evaluate the potential toxicity of imidacloprid to nontarget aquatic organisms.

Biochemical, histopathological and untargeted metabolomic analyses reveal hepatotoxic mechanism of acetamiprid to Xenopus laevis.

Acetamiprid, a commonly detected neonicotinoid in aquatic ecosystems, poses a threat to aquatic non-target organisms. However, limited information is available on the toxic effects of acetamiprid on nontarget aquatic organisms. This study assessed the toxic effects of acetamiprid on Xenopus laevis, a typical model organism. The acute toxicity for 96 h revealed that acetamiprid had detrimental effects with a median lethal concentration (LC50) value of 64.48 mg/L. Toxicity assays, including oxidative stress, histopathology and untargeted metabolomics of acetamiprid to X. laevis, were performed for 28 d at 1/10 and 1/100 LC50 by studying the liver, which is the most antioxidant and major metabolic organ. The results demonstrated that acetamiprid exposure significantly changed the oxidant status of and caused histological damage to the liver. Furthermore, the untargeted metabolomic analysis based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified the endogenous metabolites that were significantly altered. There were 89 differential metabolites compared to the controls: 64 in the 1/10 LC50 group, 47 in the 1/100 LC50 group, and 23 metabolites in the 1/10 LC50 group were the same as those in the 1/100 LC50 group. Sixteen pathways that were mainly associated with amino acid metabolism and lipid metabolism, such as sphingolipid metabolism, glycerophospholipid metabolism and histidine metabolism, were disrupted, revealing the hepatotoxic effects of acetamiprid on X. laevis at the molecular level. These findings provide crucial information for evaluating the aquatic risks of neonicotinoids.

Insight into the toxic effects, bioconcentration and oxidative stress of acetamiprid on Rana nigromaculata tadpoles.

Pesticide pollution has been identified as a factor in the amphibian population decrease. Acetamiprid is a common neonicotinoid pesticide that poses a risk to amphibians due to its high water solubility and inability to be digested. However, there is little research on acetamiprid's toxicity in amphibians, particularly on its biochemical toxic effects. In this study, we investigated the acute toxicity, bioenrichment-elimination, biochemical parameters and metabolism of acetamiprid in Rana nigromaculata tadpoles. The results indicated that acetamiprid is harmful to Rana nigromaculata tadpoles, with an LC50 = 18.49 mg L-1 of 96 h for acute toxicity. Acetamiprid showed rapid accumulation and low bioconcentration levels in tadpoles, with bioconcentration factors (BCFs) < 1. In the elimination process, the concentration of acetamiprid decreased rapidly, with the elimination half-life t1/2 values < 1 d. Additionally, oxidative stress was observed in tadpoles, with biochemical parameters such as superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) being significantly altered. Nontargeted metabolomics revealed significant changes in biomolecules such as lipids, organic acids and nucleotides in tadpoles, and these metabolites influence pathways including serine and threonine metabolism, histidine metabolism, linoleic acid metabolism and sphingolipid metabolism. These results indicate that acetamiprid caused toxic effects on Rana nigromaculata tadpoles. Our study provides a better understanding of the fate and risk of acetamiprid in amphibians, as well as guidelines for its rational use.

Insight into the differences in the toxicity mechanisms of dinotefuran enantiomers in zebrafish by UPLC-Q/TOF-MS.

Dinotefuran is a chiral insecticide widely used to control Nilaparvata lugens in agriculture. However, little is known about the toxic effects of dinotefuran enantiomers on aquatic organisms. In this study, zebrafish were exposed to 1.00 and 10.00 mg/L dinotefuran enantiomers for 96 h, after which multivariate pattern recognition, metabolite identification, and pathway analysis were performed. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were then conducted to reveal the metabolic perturbations caused by dinotefuran enantiomers. Metabolic pathway analysis revealed the perturbation of five main pathways, including phenylalanine, tyrosine and tryptophan biosynthesis; phenylalanine metabolism; retinol metabolism; arginine and proline metabolism; and glycerophospholipid metabolism. These disturbed metabolic pathways were strongly correlated with energy, amino acid metabolism, and lipid metabolism. Pathway analysis also indicated that the metabolic pathway changes induced by the same level of R and S-dinotefuran were enantioselective. Our research may provide better insight into the risk of chiral dinotefuran in aquatic organisms in the environment.